6480
S. Sharma et al. / Bioorg. Med. Chem. Lett. 21 (2011) 6476–6481
Table 7
IC50, pIC50 and Pre.pIC50 of the compounds against T. mentagrophytes
Compd no.
IC50
pIC50 (x)
Pre.pIC50 (y)
10a
10c
10d
9a
5.89
ꢀ0.770
ꢀ1.651
ꢀ1.007
0.476
ꢀ0.701
ꢀ0.874
ꢀ1.076
0.419
44.73
10.16
0.33
9d
9e
9f
9g
9h
9i
0.46
12.61
5.73
9.48
5.48
24.45
2.12
11.7
6.11
2.24
2.76
0.53
22.84
13.54
14.89
4.39
0.337
0.044
ꢀ1.101
ꢀ0.758
ꢀ0.977
ꢀ0.739
ꢀ1.388
ꢀ0.326
ꢀ1.068
ꢀ0.786
ꢀ0.351
ꢀ0.441
0.276
ꢀ0.766
-0.874
ꢀ1.140
ꢀ0.741
ꢀ1.297
ꢀ0.741
ꢀ1.032
ꢀ0.754
ꢀ0.874
0.044
9j
9k
9m
9n
9o
9p
9w
9x
9y
Figure 5. 2D scatter plot between pIC50 and Pre.pIC50 of T. mentagrophytes.
0.044
ꢀ1.359
ꢀ1.132
ꢀ1.173
ꢀ0.643
ꢀ1.492
ꢀ1.117
ꢀ1.117
ꢀ0.548
in case of S. aureus. The field (F3) parameter contributes positively
in all the three stains of fungi C. abicans, S. schenckii and T. mentag-
rophytes and HA3 contributes negatively in S. aureus,
r
1 contrib-
9z
utes negatively to S. schenckii activity and
r
2 contributes
Correlation matrix among the parameters used for deriving Eq. 5
positively to T. mentagrophytes activity. In addition the basicity of
the N atom is also important as the compounds N-Boc were more
active than their NH analogs. Thus, these studies may be useful in
the design of the compounds with more potent anti-fungal and
anti-bacterial activities.
pIC50
I
F3
R3
r2
pIC50
I
F3
1.000
0.094
0.086
ꢀ0.337
0.339
1.000
ꢀ0.180
1.000
R3
0.248
0.071
ꢀ0.404
1.000
0.343
r
2
ꢀ0.164
1.000
Acknowledgments
pIC50 ¼ 1:121 ðꢁ0:268Þ I þ 1:210 ðꢁ0:291Þ F3 ꢀ 2:418 ðꢁ0:435Þ
The authors are thankful to MOH, for providing funds, Mr. Zahid
Ali and Mr. A. S. Kushwaha for technical assistance, Mr. I. A. Khan
for valuable suggestions and SAIF division C.D.R.I. for providing
MASS, NMR and IR data. The CDRI communication number for this
manuscript is 8118.
R3 þ 5:692 ðꢁ0:974Þ ꢂ
r2 ꢀ 2:419 ðꢁ0:354Þ; N ¼ 20;
r ¼ 0:864; r2 ¼ 0:747; s ¼ 0:330; F ¼ 11:052; p ¼ 0:000:
ð5Þ
Supplementary data
Supplementary data associated with this article can be found, in
Reference and notes
1. Fact sheet no. 310; who: Geneva 2008.
2. Lass-Florl, C.; Griff, K.; Mayr, A.; Petzer, A.; Gastl, G.; Bonatti, H.; Freund, M.;
Kropshofer, G.; Dierich, M. P.; Nachbaur, D. Brit. J Haematol. 2005, 131, 201.
3. Pfaller, M. A.; Diekema, D. J. Clin. Microbiol. Rev. 2007, 20, 133.
4. Segal, B. H.; Walsh, T. J. Am. J. Respir. Crit. Care Med. 2006, 173, 707.
5. Arendrup, M. C.; Fuursted, K.; Gahrn-Hansen, B.; Jensen, I. M.; Knudsen, J. D.;
Lundgren, B.; Schonheyder, H. C.; Tvede, M. J. Clin. Microbiol. 2005, 4434, 43.
6. Enoch, D. A.; Ludlam, H. A.; Brown, N. M. J. Med. Microbiol. 2006, 55, 809.
7. Casell, G. H.; Mekalnos, J. J. Am. Med. Assoc. 2001, 285, 601.
8. White, D. G.; McDermott, P. F. J. Dairy Sci. 2001, 84, E151.
9. (a) Bax, R.; Mullan, N.; Verhoef, J. Int. J. Antimicrob. Agents. 2000, 16, 51; (b)
Heinemann, J. A.; Ankenbauer, R. G.; Amabile-Cuevas, C. F. Drug Discovery Today
2000, 5, 195.
Figure 3. 2D scatter plot between pIC50 and Pre.pIC50 of C. abicans.
10. Payne, D. J.; Gwyan, M. N.; Holmes, D. J.; Pompliano, D. L. Nat. Rev. Drug Disc.
2006, 6, 29.
11. Daicel Chemical Industries Ltd, European Patent Application No. 0 654 534 A2
November 18, 1994.
12. (a) Petrow, V.; Stephenson, O. J. Pharm. Pharmacol. 1953, 5, 359; (b) Crowther,
A. F.; Smith, L. H. J. Med. Chem. 1968, 11, 1009; (c) Hu, B.; Ellingboe, J.; Han, S.;
Largis, E.; Lim, K.; Malamas, M.; Mulvey, R.; Niu, C.; Oliphant, A.; Pelletier, J.;
Singanallore, T.; Sum, F.-K.; Tillett, J.; Wong, V. Bioorg. Med. Chem. 2001, 9,
2045.
13. Wang, Z. M.; Zhang, X. L.; Sharpless, K. B. Tetrahedron Lett. 1993, 34, 2267.
14. Kokotos, G.; Padron, J. M.; Noula, C.; Gibbons, W. A.; Martin, V. S. Tetrahedron:
Asymmetry 1996, 7, 857.
15. Tanemura, K.; Suzuki, T.; Nishida, Y.; Satsumabayashi, K.; Horaguchi, T. Chem.
Lett. 2003, 32, 932.
16. Cope, A. C.; Burrows, E. P.; Derieg, M. E.; Moon, S.; Wirth, W. D. J. Am. Chem. Soc.
1965, 87, 5452.
17. Schmid, H.; Karrer, P.; Helv Chim. Acta 1946, 29, 573.
18. Tanemura, K.; Suzuki, T.; Nishida, Y.; Satsumabayashi, K.; Horaguchi, T. Chem.
Commun. 2004, 470.
Figure 4. 2D scatter plot between pIC50 and Pre.pIC50 of S. schenckii.